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Background Serum soluble tumor necrosis factor receptor 2 ( sTNFR2) concentration predicted the clinical outcome of patients with aggressive non-Hodgkin's lymphoma including diffuse large B-cell lymphoma (DLBCL) treated with CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) in our previous study. However, after rituximab (R) was introduced in clinical practice, R-CHOP replaced CHOP as the standard therapy for DLBCL. Patients and methods In this study, we re-evaluated the prognostic significance of serum sTNFR2 in 154 patients with DLBCL treated with R-CHOP. Results Five-yr overall survival (5-yr OS) rates with sTNFR2 ≥20 ng/mL and <20 ng/mL were 29.2% and 83.3% ( P < 0.0001), respectively, and the corresponding 5-yr progression-free survival (5-yr PFS) rates were 26.9% and 76.4% ( P < 0.0001), respectively. A multivariate analysis revealed that serum sTNFR2 and complete remission (CR) were independent prognostic factors for both OS (CR: P < 0.0001, sTNFR2: P = 0.0001) and PFS (CR: P < 0.0001, sTNFR2: P = 0.0001). The prognosis of patients with poor risk groups according to the revised International Prognostic Index who also had high serum sTNFR2 was especially poor. Conclusion Serum sTNFR2 might be a powerful prognostic factor for patients with DLBCL in the rituximab era. [ABSTRACT FROM AUTHOR]

Waldenström's macroglobulinemia (WM) is a slowly progressive, low-grade B cell lymphoproliferative disorder. In contrast to the indolent progression, the development of cryoglobulinemic glomerulonephritis associated with WM is a rare, aggressive, and life-threatening complication. We describe the case of a 53-year-old man who suffered from WM, which was accompanied by cryoglobulinemic glomerulonephritis. WM was diagnosed on the basis of an increase in monoclonal IgM kappa and infiltration of abnormal lymphoplasmacytic cells in the bone marrow. Moreover, the case was complicated by increase in the levels of urinary protein, serum creatinine, and serum cryoglobulin. Histological findings showed endocapillary glomerulonephritis with hyaline plugs. Electron microscopy demonstrated the accumulation of electron-dense deposits in the subepithelial, subendothelial, intramembranous, and mesangial areas, which revealed cryoglobulinemic proliferative glomerulonephritis. The patient received four courses of rituximab therapy followed by four courses of R-CHOP therapy (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) in combination with cryofiltration. Subsequently, the patient underwent high-dose chemotherapy (melphalan [L-PAM]) followed by tandem autologous peripheral blood stem cell transplantation. After these treatments, the patient remained disease-free for 26 months. Histological findings of cryoglobulinemic glomerulonephritis were markedly improved after these treatments. Our case suggests that these treatments may be a feasible, safe, and effective strategy for critical cryoglobulinemic glomerulonephritis derived from WM. [ABSTRACT FROM AUTHOR]

The prognostic significance of O6-methylguanine DNA methyltransferase (MGMT) inactivation was evaluated in patients with diffuse large B-cell lymphoma (DLBCL) who received cyclophosphamide, doxorubicin, vincristine, and prednisone (CHOP) in addition to rituximab. In this retrospective study, we used the methylation-specific polymerase chain reaction to investigate MGMT promoter methylation status and immunohistochemistry to evaluate MGMT expression in patients with DLBCL who received rituximab plus CHOP (R-CHOP) chemotherapy. No difference in patient characteristics, disease characteristics, response, or survival in patients with DLBCL who received front-line R-CHOP chemotherapy was observed according to MGMT methylation status and MGMT expression. On multivariate analysis, Grade 3–4 mucositis in the MGMT methylated group was significantly higher than that in the MGMT unmethylated group (hazard ratio (HR) 2.40, 95% CIs: 1.26–7.26, p = 0.014). This study demonstrated that inactivation of MGMT does not appear to play an important role in patients with DLBCL who received R-CHOP chemotherapy either with regard to the response rate or overall survival. Additionally, Grade 3–4 mucositis was found to be significantly related with inactivation of MGMT by a multivariate analysis. [ABSTRACT FROM AUTHOR]

Introduction: Diffuse Large B-cell Lymphoma (DLBCL) is the most common aggressive non-Hodgkin lymphoma (NHL), with an incidence in Europe of 3.8/100.000/year. A multi-drugs chemoimmunotherapy regimen, containing rituximab, cyclophosphamide, vincristine, doxorubicin and prednisone (R-CHOP) administrated every 21 days, is the standard therapy for DLBCL patients. The discovery of several biological features of DLBCL has encouraged the introduction of novel drugs in the treatment. Areas covered: In this article, the use of standard therapies will be reviewed and will be investigated adoption of novel drugs such as Bortezomib, Bruton's tyrosine kinase, IMiDs, Venetoclax, mTOR inhibitors and other biological agents. Expert commentary: A better knowledge of the biology of DLBCL is mandatory to tailor treatment and to ameliorate the poor prognosis of DLBCL. The addition of novel drugs to standard RCHOP should represent a modern approach in the treatment of DLBCL. Ibrutinib and lenalidomide showed important results in DLBCL and the integration of these drugs in first line treatment is under investigation. Despite encouraging results using novel drugs in the setting of relapsed/refractory DLBCL, the rate of failures still remains at 40%; for these reason, continued participation in clinical trials should be encouraged.

Introduction: Diffuse large B-cell lymphoma (DLBCL) is the most common histotype in non Hodgkin lymphoma, with a peak incidence in the sixth decade. The standard treatment for elderly FIT DLBCL patients is Rituximab-CHOP; in unfit and frail patients, chemotherapy at reduced intensity should be considered. Areas covered: In this article, we will review use of standard therapies and new drugs investigated such as immonomudulating agents (IMiDs), Bruton Tyrosine Kinase (BTK), in fit, unfit, frail and very elderly DLCBL patients. Expert commentary: R-CHOP21 in fit DLBCL patients is still the standard of care, while in elderly unfit patients a reduction of doses of cytotoxic drugs or schemes that avoid antracycline should be considered. The Comprensive Geriatric Assesment based in age, comorbidities and functional abilities of daily living is an important tool in elderly, in order to discriminate between fit, unfit or frail patients. Novel drugs represent valid therapeutic options in relapsed/refractory setting so continued participation in clinical trials should be encouraged.

Diffuse large B-cell lymphoma (DLBCL) represents the most common lymphoid malignancy in adults, with a median age of 60 to 70 years. Clinical behavior is usually rapidly aggressive, with extranodal involvement in 40% of cases. Chemoimmunotherapy administered every 21 days is still the standard of care in the advanced stage. Optimization of frontline therapy and the amelioration of salvage strategies remain the most important targets in the treatment of patients with DLBCL. Novel drugs directed to specific molecular targets have been introduced as single agents or in addition to standard chemoimmunotherapy for the treatment of DLBCL., (Copyright © 2016 Elsevier Inc. All rights reserved.)